Variable‐Constant Segment Genotype of Immunoglobulin Kappa is Associated with Increased Risk for Rheumatoid Arthritis

Abstract

Objective. To further investigate the association of rheumatoid arthritis (RA) with a particular genotype identified by a restriction site polymorphism near the constant segment of immunoglobulin kappa (C,).Methods. The frequencies of genomic DNA polymorphisms detected within or near C, (the most C, -proximal variable segment [V,] B3 and a T lymphocyte marker [CDSA]) were determined by Southern blotting and hybridization. The frequencies of coding-region polymorphisms of C, (Km allotypes) were determined by amplification by polymerase chain reaction followed by restriction enzyme digestion.Results. Although the frequencies of B3, Km, and CD8A genotypes were not Merent between RA and normal control populations, more individuals were homozygous for both C, and B3 in the RA group (relative risk 2.2, P < 0.01), especially in the DR4-negative RA subgroup (relative risk 3.9, P < 0.001).

Identification of a new non‐major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen‐induced arthritis in rats

“…MHC-related genes are also the major genetic loci controlling CIA susceptibility and severity in rats (16,17). Very little is known about the non-MHC genes in RA and other human autoimmune diseases (7)(8)(9)(42)(43)(44)(45)(46). It is suspected that many non-MHC genes are involved, each with a rclatively small effect on disease expression.…”

“…A strong gcnetic contribution to susceptibility, most likely under non-Mendelian polygenic control, is evident from family studies (1). Although several biochemical pathways have been implicated in the pathogenesis of RA, very few susceptibility-and severity-controlling genes/ loci have been conclusively identified (2)(3)(4)(5)(6)(7)(8)(9). HLAaswciated genes are the most thoroughly documented and may account for as much ac 50% of the total genetic contribution to RA susceptibility (2).…”

“…HLA genes may also regulate discasc sevcrity (2,5,6). There is little definitive knowledge about non-major histocompatibility complex (non-MHC) genes in RA (7)(8)(9). Moreover, little is known about how sex regulates disease expression.…”

Characterization of a germline Vk gene encoding cationic anti-DNA antibody and role of receptor editing for development of the autoantibody in patients with systemic lupus erythematosus.

“…Moreover, it is reported that there are at least 16 polymorphisms and 9 haplotypes in the Vk cluster of normal individuals (10). It has been reported that certain polymorphisms within the human Ig Vk locus are associated with rheumatoid arthritis (11,12). In addition, it has been shown that polymorphisms in the two human VH genes, both of which can encode anti-DNA Abs are related with the development of autoimmune diseases (13)(14)(15).…”

Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats

“…A strong gcnetic contribution to susceptibility, most likely under non-Mendelian polygenic control, is evident from family studies (1). Although several biochemical pathways have been implicated in the pathogenesis of RA, very few susceptibility-and severity-controlling genes/ loci have been conclusively identified (2)(3)(4)(5)(6)(7)(8)(9). HLAaswciated genes are the most thoroughly documented and may account for as much ac 50% of the total genetic contribution to RA susceptibility (2).…”